At the present time, over 12 million units of whole blood are collected from volunteer donors in the United States each year. Because of the advent of blood component therapy, approximately 60% to 80% of the whole blood collected today is not itself stored and used for transfusion. Instead, the whole blood is first separated into its clinically proven components, which are themselves individually stored and used to treat a multiplicity of specific conditions and diseased states.
The clinically proven components of whole blood include red blood cells, which can be used to treat chronic anemia; platelet-poor plasma, from which Clotting Factor VIII-rich cryoprecipitate can be obtained for the treatment of hemophilia; and concentrations of platelets, which can be used to control thrombocytopenic bleeding.
The present medical consensus is that care of a patient is improved by providing only the therapeutic components of whole blood which are required to treat the specific disease. The demand for therapeutic components of whole blood is thus ever-increasing. Likewise, the demand for safe and effective systems and methods for collecting, separating, and storing the therapeutic components of whole blood grows accordingly.
One desirable feature for a blood collection and separation system and method is the capability to maximize, to the greatest extent possible, the yield of clinically proven blood components during a single collection procedure.
Minimum yield requirements for certain components are often prescribed by governmental regulations. For example, in the United States, Federal Regulations [Title 21 C.F.R. .sctn.640.24(c)] require the presence, per therapeutic unit of platelets, of at least 5.5.times.10.sup.10 platelets in at least 75% of the units tested. Typically, a unit of platelets includes, as a suspension media, about 50 milliliters of plasma.
Another desirable feature for a blood collection and separation system and method is the capability of yielding components which are suited for storage for prolonged periods. This feature is closely related to the degree of sterility a given blood collection system can assure. Such matters are also usually the subject of governmental regulations.
For example, in the United States, whole blood and components which are collected and processed in a nonsterile, or "open", system must be transfused within twenty-four (24) hours of collection. On the other hand, in the United States, whole blood and red cells which are collected in a sterile, or "closed", system may be stored for upwards to thirty-five days, depending upon the type of anticoagulant and storage medium used. Likewise, platelets which are collected in a "closed" system may be stored for upwards to five days, and possibly longer, depending upon the ability of the storage container to maintain proper storage conditions. Plasma which is collected in a "closed" system may be frozen for even more prolonged storage periods.
In the United States, Federal Regulations [Title 21 C.F.R. .sctn.640.16(b)] define a "closed" blood collection system as one in which the initially sterile blood collection and transfer containers are integrally attached to each other and not open to communication with the atmosphere. Furthermore, to remain a "closed" blood collection system in the United States, the blood collection container of the system cannot be "entered" in a non-sterile fashion after blood collection. An entry into a blood collection system which presents the probability of non-sterility which exceeds one in a million (i.e., greater than 10.sup.-6) is generally considered in the United States to constitute a "non-sterile" entry.
Representative examples of known whole blood collection assemblies include the following U.S. Patents:
______________________________________ Earl 3,064,647 Wandell et al 3,078,847 Bellamy Jr. 3,110,308 Tenczar Jr. 3,187,750 Viguier 3,870,042 Garber et al 3,986,506 Djerassi 4,111,199 Smith 4,222,379 ______________________________________
Representative examples of known commercially available whole blood collection assemblies are sold by Fenwal Laboratories, Inc. (a division of Travenol Laboratories, Inc., Deerfield, Ill.); Delmed Corp., Irvine, Calif.; and Cutter Laboratories, Inc., Berkeley, Calif.
All of the above-identified blood collection assemblies rely exclusively upon nonautomated batch centrifugation procedures to separate the collected unit of whole blood (approximately 450 milliliters) into its various components.
During conventional batch centrifugation, the collected unit of whole blood is first subjected to a centrifugal force for a period of time sufficient to initially separate the whole blood into red blood cells and plasma in which substantial amounts of platelets are present (known as platelet-rich plasma). This step of the procedure is commonly referred to as the "soft spin".
The platelet-rich plasma is then manually expressed into another container and subjected to a greater centrifugal force for generally a longer period of time to further separate the platelet-rich plasma into platelet concentrate and platelet-poor plasma. This step of the procedure is commonly referred to as the "hard spin".
During the course of nonautomated batch centrifugation, approximately 100 milliliters of plasma otherwise suited for storage or further fractionation is "lost", because some of it remains with the red blood cells after the soft spin, and some of it is transferred along with the platelets after the hard spin. Therefore, using conventional batch centrifugation, plasma yields cannot be optimized.
Furthermore, as the authors observe in S. J. Slichter et al, "Preparation and Storage of Platelet Concentrates (Factors Influencing the Harvest of Viable Platelets from Whole Blood)", British Journal of Haematology, 1976, 34, 395-402, "accurate, standardized centrifugation procedures are critical for efficient preparation of platelet concentrates". To harvest 86% of the platelets from a unit of whole blood without loss of viability, the authors recommend (on page 401 of the article) a soft spin of 1000 g (i.e., one thousand times the force of gravity) for 9 minutes, followed by a hard spin of 3000 g for 20 minutes.
Centrifugal procedures which optimize platelet yields thus tend to be time consuming. Furthermore, because skilled technicians are required to calibrate and operate the centrifuges used during these procedures, nonautomated batch centrifugation also tends to be labor intensive.
Additionally, because platelets will lose viability if spun too hard and/or too long, it is extremely difficult, if not impossible, to create centrifugal forces during a conventional hard spin sufficient to separate virtually all of the platelets from the plasma. For example, the Slichter et al article observes (on page 397) that platelet-poor plasma obtained during conventional batch centrifugation techniques includes platelets present in a concentration of between 13,000 and 16,000 platelets per microliter.
The inability of conventional batch centrifugation techniques to yield virtually platelet-free plasma leads to further inefficiencies in blood component processing.
For example, it has been observed that the presence of platelets in the plasma from which Clotting Factor VIII-rich cryoprecipitate is obtained reduces the effective yields of the Factor VIII. Thus, platelet-poor plasma obtained by conventional batch centrifugation techniques does not maximize, to the greatest extent possible, the yield of Factor VIII.
Furthermore, the measurable presence of platelets in platelet-poor plasma means, of course, that these platelets are not present in the platelet concentrate. Thus, conventional batch centrifugation techniques do not maximize, to the greatest extent possible, the yield of platelet concentrate.
Therefore, another desirable feature of blood collection and separation systems and methods is the ability to obtain optimal yields of platelets and virtually platelet-free plasma.
A novel blood collection system which is capable of optimizing component yields using exclusively nonautomated batch centrifugation techniques is disclosed in copending Ronald A. Williams et al, U.S. patent application No. 373,555, filed Apr. 30, 1982, and entitled INCREASED YIELD BLOOD COLLECTION SYSTEMS AND METHODS, now abandoned which is a continuation-in-part of U.S. patent application No. 316,918, filed Oct. 30, 1981, now abandoned.
A novel blood collection system which is capable of optimizing component yields and attendant storage times using a "continuous flow" centrifugation technique is disclosed in Ronald A. Williams et al, patent application No. 403,832 (filed July 30, 1982) and entitled INCREASED YIELD CONTINUOUS FLOW BLOOD COMPONENT COLLECTION SYSTEM now abandoned.
Novel blood collection systems and methods which utilize a microporous membrane to perform all or part of an extended yield blood collection procedure are disclosed in Bloom et al U.S. patent application Ser. No. 766,664, filed Aug. 15, 1985, entitled "Increased Yield Blood Component Collection Systems and Methods" now abandoned, which is a continuation of U.S. patent application Ser. No. 641,345, filed Aug. 15, 1984 now abandoned, which is a continuation of U.S. patent application Ser. No. 411,056, filed Aug. 24, 1982, now abandoned; as well as in Bilstad et al. U.S. patent application Ser. No. 690,399, filed Jan. 9, 1985, entitled "Increased Yield Blood Component Collection Systems and Methods", which is a continuation of U.S. patent application Ser. No. 411,057, filed Aug. 24, 1982 now abandoned. The parent applications of these two cases share the same earliest filing date as the now abandoned parent of the instant application.
With the foregoing considerations in mind, one of the principal objects of this invention is to provide blood collection systems and methods which maximize, to the greatest extent possible, the yield of blood components obtained during a single collection procedure in a manner which also assures the maximum available storage period for each of the components collected, as measured by applicable United States standards.
Another principal object of this invention is to provide blood collection systems and methods which, in addition to the above-described attributes, provides plasma which is virtually platelet-free.
Yet another principal object of this invention is to provide blood collection systems and methods which, in addition to any of the above-described attributes, minimizes, to the greatest extent possible, the overall time involved during a given procedure.
Yet another one of the principal objects of this invention is to provide blood collection systems and methods which, in addition to the just described attributes, need not depend entirely upon costly, relatively large, and sophisticated processing devices.